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While UK-93,928 (1-[[3-(6,9-dihydro-6-oxo-9-propyl-1H-purin-2-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine; 5 nM-5 microM) was devoid of relaxant activity, benzafentrine, isoprenaline, levcromakalim and SCA40 (6-bromo-8-methylaminoimidazo[1,2-a]pyrazine-2-carbonitrile) each relaxed histamine (460 microM)-precontracted bovine isolated trachealis. Each of these relaxants was antagonised by a K+-rich (80 mM) medium. Except in the case of levcromakalim, nifedipine (1 microM) offset this antagonism. Charybdotoxin (100 nM) antagonised isoprenaline in a nifedipine-sensitive manner but did not antagonise SCA40 or benzafentrine. Iberiotoxin (100 nM) did not antagonise SCA40. Acting on tissue precontracted with carbachol, SCA40 potentiated isoprenaline but did not potentiate sodium nitroprusside. While levcromakalim (1 and 10 microM) induced hyperpolarisation, SCA40 (1 and 10 microM) induced little change in the membrane potential of bovine trachealis. In trachealis preloaded with 86Rb+, levcromakalim (1 and 10 microM) promoted efflux of the radiotracer while SCA40 (1 and 10 microM) had no effect. Tested as an inhibitor of isoenzymes of cyclic nucleotide phosphodiesterase, SCA40 was most potent against the type III, less potent against the type IV and least potent against the type I isoenzyme. It is concluded that neither inhibition of phosphodiesterase type V nor the promotion of BKCa channel opening explains the tracheal smooth muscle relaxant activity of SCA40. This compound relaxes bovine tracheal smooth muscle mainly by inhibiting phosphodiesterase isoenzyme types III and IV.
T M Pocock, and
F Laurent, and
L M Isaac, and
P Chiu, and
K R Elliott, and
R W Foster, and
A Michel, and
P A Bonnet, and
R C Small
May 2017,
Cellular and molecular life sciences : CMLS,
T M Pocock, and
F Laurent, and
L M Isaac, and
P Chiu, and
K R Elliott, and
R W Foster, and
A Michel, and
P A Bonnet, and
R C Small
May 1973,
Biochemical and biophysical research communications,
T M Pocock, and
F Laurent, and
L M Isaac, and
P Chiu, and
K R Elliott, and
R W Foster, and
A Michel, and
P A Bonnet, and
R C Small
January 1996,
Annual review of pharmacology and toxicology,
T M Pocock, and
F Laurent, and
L M Isaac, and
P Chiu, and
K R Elliott, and
R W Foster, and
A Michel, and
P A Bonnet, and
R C Small
April 1992,
Journal of cardiovascular pharmacology,
T M Pocock, and
F Laurent, and
L M Isaac, and
P Chiu, and
K R Elliott, and
R W Foster, and
A Michel, and
P A Bonnet, and
R C Small
January 1986,
Progress in clinical and biological research,
T M Pocock, and
F Laurent, and
L M Isaac, and
P Chiu, and
K R Elliott, and
R W Foster, and
A Michel, and
P A Bonnet, and
R C Small
November 2001,
The Journal of allergy and clinical immunology,
T M Pocock, and
F Laurent, and
L M Isaac, and
P Chiu, and
K R Elliott, and
R W Foster, and
A Michel, and
P A Bonnet, and
R C Small
January 1973,
Advances in cyclic nucleotide research,
T M Pocock, and
F Laurent, and
L M Isaac, and
P Chiu, and
K R Elliott, and
R W Foster, and
A Michel, and
P A Bonnet, and
R C Small
January 1984,
Advances in cyclic nucleotide and protein phosphorylation research,
T M Pocock, and
F Laurent, and
L M Isaac, and
P Chiu, and
K R Elliott, and
R W Foster, and
A Michel, and
P A Bonnet, and
R C Small
January 1977,
Advances in cyclic nucleotide research,
T M Pocock, and
F Laurent, and
L M Isaac, and
P Chiu, and
K R Elliott, and
R W Foster, and
A Michel, and
P A Bonnet, and
R C Small
July 1978,
Biochemical and biophysical research communications,
